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Jun.2.2020

Elsevier Drug Monographs

Ruxolitinib

Indications/Dosage

Labeled

  • graft-versus-host disease (GVHD)
  • myelofibrosis
  • polycythemia vera

Off-Label

  • coronavirus disease 2019 (COVID-19)
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
† Off-label indication

For the treatment of polycythemia vera

The FDA has designated ruxolitinib as an orphan drug for the treatment of polycythemia vera.

INVESTIGATIONAL USE: For adjunctive use in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection†, the virus that causes coronavirus disease 2019 (COVID-19)†

Oral dosage

Adults

Efficacy has not been established. Due to broad immunosuppressive effects, the National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of JAK inhibitors outside of clinical trials.[65314] The following dosing regimens are being evaluated: 5 mg PO twice daily [65302] [65499]; 5 mg PO twice daily for 14 to 28 days [65356]; 5 mg PO every 12 hours for 7 days, then 10 mg PO every 12 hours for a total of 14 days [65304]; 10 mg PO twice daily for 14 days, then 5 mg PO twice daily for 2 days, then 5 mg PO once daily for 1 day [65303]; 10 mg PO twice daily for 14 days [65301]; and 10 to 20 mg PO twice daily for 7 days [65300].

Children and Adolescents 12 years and older

Efficacy has not been established. Due to broad immunosuppressive effects, the National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of JAK inhibitors outside of clinical trials.[65314] The following dosing regimens are being evaluated: 5 mg PO twice daily for 14 to 28 days [65356]; 10 mg PO twice daily for 14 days, then 5 mg PO twice daily for 2 days, then 5 mg PO once daily for 1 day.[65303]

For the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis

NOTE: Patients experiencing significant decreases in platelet counts may be candidates for abrupt dose reductions and/or treatment interruptions. Consider risk to benefits ratio in patients maintained on 5 mg PO twice daily (minimum dose) as long-term use at this dose has failed to produce clinical response.[46782]

Oral dosage

Adults with initial platelet count more than 200 x 10(9) cells/L

20 mg PO twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. After the first 4 weeks of therapy, and no more frequently than every 2 weeks, the dose may be increased in 5 mg twice daily increments to a maximum dose of 25 mg PO twice daily if the patient meets all of the following criteria: 1) failure to achieve a reduction from baseline palpable spleen length of 50% or a 35% reduction in spleen volume as measured by CT or MRI; 2) platelet count more than 125 x 109 cells/L at treatment week 4 and platelet counts never less than 100 x 109 cells/L; 3) absolute neutrophil count (ANC) more than 0.75 x 109 cells/L. Discontinue ruxolitinib if spleen size reduction or symptom improvement is not observed after 6 months of therapy. When discontinuing therapy for any reason other than thrombocytopenia, consider gradually tapering dose by 5 mg twice daily each week.[46782]

Adults with initial platelet count of 100 to 200 x 10(9) cells/L

15 mg PO twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. After the first 4 weeks of therapy, and no more frequently than every 2 weeks, the dose may be increased in 5 mg twice daily increments to a maximum dose of 25 mg PO twice daily if the patient meets all of the following criteria: 1) failure to achieve a reduction from baseline palpable spleen length of 50% or a 35% reduction in spleen volume as measured by CT or MRI; 2) platelet count more than 125 x 109 cells/L at treatment week 4 and platelet counts never less than 100 x 109 cells/L; 3) absolute neutrophil count (ANC) more than 0.75 x 109 cells/L. Discontinue ruxolitinib if spleen size reduction or symptom improvement is not observed after 6 months of therapy. When discontinuing therapy for any reason other than thrombocytopenia, consider gradually tapering dose by 5 mg twice daily each week.[46782]

Adults with initial platelet count of 50 to 99 x 10(9) cells/L

5 mg PO twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. After the first 4 weeks of therapy, and no more frequently than every 2 weeks, the dose may be increased in 5 mg daily increments to a maximum dose of 10 mg PO twice daily if the patient meets all of the following criteria: 1) platelet count has remained more than 40 x 109 cells/L and has not fallen by more than 20% in prior 4 weeks; 2) absolute neutrophil count (ANC) more than 1 x 109 cells/L; 3) dose has not been reduced or interrupted for an adverse event or hematological toxicity in the prior 4 weeks. Consider risk to benefits ratio in patients continuing treatment for more than 6 months. Discontinue ruxolitinib if spleen size reduction or symptom improvement is not observed after 6 months of therapy.[46782]

For the treatment of graft-versus-host disease (GVHD)

NOTE: The FDA has designated ruxolitinib as an orphan drug for the treatment of GVHD.

Therapeutic Drug Monitoring

Management of Treatment-Related Toxicity

Myelofibrosis:

Thrombocytopenia

NOTE: Hold ruxolitinib regardless of platelet count for bleeding that requires intervention. In this situation, treatment may be resumed once bleeding has resolved; consider a lower dose if the underlying cause of bleeding persists.

Baseline platelet count of 100 X 109 cells/L or higher:

  • Current platelet count of 125 X 109 cells/L or higher: No dose adjustment. If restarting after a treatment interruption for thrombocytopenia, begin with a dose at least 5 mg twice daily less than the dose when held (maximum 20 mg twice daily).
  • Current platelet count of 100 to 124 X 109 cells/L: Decrease dose by 5 mg twice daily; no dose adjustment if original dose was 15 mg twice daily or less. If restarting after a treatment interruption for thrombocytopenia, begin with a dose at least 5 mg twice daily less than the dose when held (maximum 15 mg twice daily).
  • Current platelet count of 75 to 99 X 109 cells/L: Decrease dose to 10 mg twice daily; no dose adjustment if original dose was 10 mg twice daily or less. If restarting after a treatment interruption for thrombocytopenia, begin with a dose at least 5 mg twice daily less than the dose when held (maximum 10 mg twice daily; if stable for at least 2 weeks, may increase to 15 mg twice daily).
  • Current platelet count of 50 to 74 X 109 cells/L: Decrease dose to 5 mg twice daily; no dose adjustment if original dose was 5 mg twice daily. If restarting after a treatment interruption for thrombocytopenia, begin with a dose at least 5 mg twice daily less than the dose when held (maximum 5 mg twice daily; if stable for at least 2 weeks, may increase to 10 mg twice daily).
  • Current platelet count of less than 50 X 109 cells/L: Hold ruxolitinib. May restart treatment (dose dependent on platelet count) when platelets recover to greater than 50 X 109 cells/L.

Baseline platelet count of 50 to 99 X 109 cells/L:

  • Current platelet count of 25 to 35 X 109 cells/L and platelet decline during prior 4 weeks is less than 20%: Decrease total daily dose by 5 mg; for patients on 5 mg daily before platelet decline, continue same dose.
  • Current platelet count of 25 to 35 X 109 cells/L and platelet decline during prior 4 weeks is 20% or higher: Decrease dose by 5 mg twice daily; for patients taking 5 mg twice daily, decrease dose to 5 mg daily; for patients taking 5 mg daily, continue same dose.
  • Current platelet count of less than 25 X 109 cells/L: Hold ruxolitinib. May restart therapy when platelets greater than 35 X 109 cells/L, starting with a dose at least 5 mg twice daily less than the dose when held, or 5 mg daily (whichever is less).

Neutropenia

For an absolute neutrophil count (ANC) of less than 0.5 X 109 cells/L: Hold ruxolitinib. When ANC greater than 0.75 X 109 cells/L, may restart treatment at 5 mg twice daily below the largest dose in the week prior to holding therapy, or 5 mg daily (whichever is higher).

Polycythemia Vera:

Hematologic Toxicity

  • Hemoglobin level of 12 grams/dL or higher AND a platelet count of 100 X 109 cells/L or higher: No dosage adjustment required.
  • Hemoglobin level of 10 to 11 grams/dL AND a platelet count of 75 to 99 X 109 cells/L: Consider a dosage reduction.
  • Hemoglobin level of 8 to 9 grams/dL OR a platelet count of 50 to 74 X 109 cells/L: Reduce the current ruxolitinib dosage by 5 mg twice daily; if the current dosage is 5 mg twice daily, reduce the dosage to 5 mg once daily.
  • Hemoglobin level of less than 8 grams/dL OR a platelet count of less than 50 X 109 cells/L OR an ANC of less than 1 X 109 cells/L: Hold ruxolitinib until hematologic parameters are recovered to acceptable levels.

Determining the Maximum Restarting Dosage:

NOTE: Following therapy interruption, the final titrated daily dosage should not exceed 5 mg less than the held dosage. The exception is for dose interruption after phlebotomy-associated anemia; the maximum total daily dose in this case would be 25 mg twice daily.

  • Hemoglobin level of 8 to 9 grams/dL OR a platelet count of 50 to 74 X 109 cells/L OR an ANC of 1 to 1.4 X 109 cells/L: The restarting ruxolitinib dosage is 5 mg twice daily (may be increased by 5 mg twice daily if hematologic parameters are still stable after 2 weeks) or no more than 5 mg twice daily less than the held dosage.
  • Hemoglobin level of 10 to 11 grams/dL OR a platelet count of 75 to 99 X 109 cells/L OR an ANC of 1.5 to 2 X 109 cells/L: The restarting ruxolitinib dosage is 10 mg twice daily (may be increased by 5 mg twice daily if hematologic parameters are still stable after 2 weeks) or no more than 5 mg twice daily less than the held dosage.
  • Hemoglobin level of 12 grams/dL or higher OR a platelet count of 100 X 109 cells/L or higher OR an ANC of greater than 2 X 109 cells/L: The restarting ruxolitinib dosage is 15 mg twice daily (may be increased by 5 mg twice daily if hematologic parameters are still stable after 2 weeks) or no more than 5 mg twice daily less than the held dosage.
  • Patients receiving 5 mg twice daily when therapy was held: may restart at 5 mg once or 5 mg twice daily when the hemoglobin level is 10 grams/dL or higher the platelet count is 75 X 109 cells/L or higher, AND the ANC is 1.5 X 109 cells/L or higher.

Graft-Versus-Host Disease (GVHD):

Hematologic Toxicity

Clinically significant thrombocytopenia after supportive measures: Reduce the current ruxolitinib dosage by 5 mg twice daily; if the current dosage is 5 mg twice daily, reduce the dosage to 5 mg once daily. Resume therapy at the prior dosage when the platelet counts recover to previous values.
ANC less than 1 X 109 cells/L (considered related to therapy): Hold ruxolitinib for up to 14 days and then resume at a reduced dosage (i.e., from 10 mg twice daily to 5 mg twice daily or from 5mg twice daily to 5 mg once daily).

Dosage Adjustments with strong CYP3A4 inhibitors or fluconazole doses 200 mg or less (Myelofibrosis or Polycythemia Vera)

NOTE: Avoid the use of ruxolitinib with fluconazole doses greater than 200 mg/day.

Stable on ruxolitinib 10 mg PO twice daily or more: Reduce ruxolitinib dose by 50%, rounding up to the closest available tablet strength. Additional dose modification should be made with careful monitoring of safety and efficacy.

Stable on ruxolitinib 5 mg PO twice daily: Reduce ruxolitinib dose to 5 mg PO once daily. Additional dose modification should be made with careful monitoring of safety and efficacy.

Stable on ruxolitinib 5 mg PO once daily: Avoid the use of strong CYP3A4 inhibitors or fluconazole treatment. Alternatively, interrupt ruxolitinib therapy for the duration of strong CYP3A4 inhibitor or fluconazole use.[46782]

Maximum Dosage Limits

  • Adults

    Myelofibrosis or Polycythemia Vera, 25 mg PO twice daily; Graft-Versus-Host Disease, 10 mg PO twice daily.

  • Geriatric

    Myelofibrosis or Polycythemia Vera, 25 mg PO twice daily; Graft-Versus-Host Disease, 10 mg PO twice daily.

  • Adolescents

    Graft-Versus-Host Disease, 10 mg PO twice daily.

  • Children

    12 years: Graft-Versus-Host Disease, 10 mg PO twice daily.

    11 years and younger: Safety and efficacy have not been established.

  • Infants

    Safety and efficacy have not been established.

  • Neonates

    Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

Myelofibrosis

Mild, moderate, or severe (Child-Pugh class A, B, C) hepatic impairment at baseline:

  • Platelet count greater than 150 X 109 cells/L: No dosage adjustment needed.
  • Platelet count of 100 to 150 X 109 cells/L: Initial dosage, 10 mg PO twice daily.
  • Platelet count of 50 to 99 X 109 cells/L: Initial dosage, 5 mg PO once daily.
  • Platelet count less than 50 X 109 cells/L: Avoid use.

Polycythemia Vera (any platelet count)

Mild, moderate, or severe (Child-Pugh class A, B, C) hepatic impairment at baseline: Initial dosage, 5 mg PO twice daily.

Graft-Versus-Host Disease (GVHD) (any platelet count)

Mild, moderate, or severe (NCI criteria) hepatic impairment at baseline: No dosage adjustment needed in patients with no liver GVHD; monitor blood counts more frequently and consider an initial dosage of 5 mg PO once daily in patients with grade 3 or 4 liver GVHD.

Management of Treatment-Related Toxicity in Patients with GVHD

No liver GVHD

Total bilirubin level of 3- to 5-times the upper limit of normal (ULN): Continue therapy at a reduced dosage (i.e., from 10 mg twice daily to 5 mg twice daily or from 5mg twice daily to 5 mg once daily) until toxicity recovery.
Total bilirubin level of greater than 5- to 10-times the ULN: Hold ruxolitinib for up to 14 days; resume therapy at the current dosage when the bilirubin level is 1.5-times the ULN or less.
Total bilirubin level of greater than 10-times the ULN: Hold ruxolitinib for up to 14 days; resume therapy at a reduced dosage (i.e., from 10 mg twice daily to 5 mg twice daily or from 5mg twice daily to 5 mg once daily) when the bilirubin level is 1.5-times the ULN or less.

Liver GVHD:

Total bilirubin level greater than 3-times the ULN: Continue therapy at a reduced dosage (i.e., from 10 mg twice daily to 5 mg twice daily or from 5mg twice daily to 5 mg once daily) until toxicity recovery.[46782]

Patients with Renal Impairment Dosing

Myelofibrosis

Creatinine Clearance (CrCl) 60 mL/min or higher: No dosage adjustment needed.

CrCl 15 to 59 mL/min:

  • Platelet count greater than 150 X 109 cells/L: No dosage adjustment needed.
  • Platelet count of 100 to 150 X 109 cells/L: Initial dosage, 10 mg PO twice daily.
  • Platelet count of 50 to 99 X 109 cells/L: Initial dosage, 5 mg PO once daily.
  • Platelet count less than 50 X 109 cells/L: Avoid use.

CrCl less than 15 mL/min, end-stage renal disease (ESRD) on intermittent dialysis:

  • Platelet count greater than 200 X 109 cells/L: Initial dose, 20 mg PO once after dialysis. Make dose modifications based on frequent monitoring of safety and efficacy.
  • Platelet count of 100 to 200 X 109 cells/L: Initial dose, 15 mg PO once after dialysis. Make dose modifications based on frequent monitoring of safety and efficacy.

CrCl less than 15 mL/min, ESRD and NOT on dialysis: Avoid use.

Polycythemia Vera (any platelet count)

CrCl 60 mL/min or higher: No dosage adjustment needed.

CrCl 15 to 59 mL/min: Initial dosage, 5 mg PO twice daily.

CrCl less than 15 mL/min, ESRD on intermittent dialysis: Initial dose, 10 mg PO once after dialysis. Make dose modifications based on frequent monitoring of safety and efficacy.

CrCl less than 15 mL/min, ESRD and NOT on dialysis: Avoid use.

Graft-Versus-Host Disease (any platelet count)

CrCl 60 mL/min or higher: No dosage adjustment needed.

CrCl 15 to 59 mL/min: Initial dosage, 5 mg PO once daily.

CrCl less than 15 mL/min, ESRD on intermittent dialysis: Initial dose, 5 mg PO once after dialysis. Make dose modifications based on frequent monitoring of safety and efficacy.

CrCl less than 15 mL/min, ESRD and NOT on dialysis: Avoid use.[46782]

† Off-label indication
Revision Date: 06/02/2020, 09:52:16 AM

References

46782 - Jakafi (ruxolitinib) tablets package insert. Wilmington, DE: Incyte Corporation; 2020 Jan.58808 - Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med 2015;372(5):426-435.65300 - Hochhaus A. Ruxolitinib in COVID-19 Patients With Defined Hyperinflammation (RuxCoFlam). Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04338958?term=Ruxolitinib&cond=COVID&draw=2&rank=365301 - University of Colorado, Denver. Safety and Efficacy of Ruxolitinib for COVID-19. Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04348071?term=Ruxolitinib&cond=COVID&draw=2&rank=165302 - Grupo Cooperativo de Hemopatias Malignas. Treatment of SARS Caused by COVID-19 With Ruxolitinib. Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04334044?term=Ruxolitinib&cond=COVID&draw=2&rank=265303 - University Health Network, Toronto. Study of the Efficacy and Safety of Ruxolitinib to Treat COVID-19 Pneumonia. Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04331665?term=Ruxolitinib&cond=COVID&draw=2&rank=565304 - Fundacion de investigacion HM. Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19. (Ruxo-Sim-20). Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04348695?term=Ruxolitinib&cond=COVID&draw=2&rank=665314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed October 9, 2020. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.65356 - Novartis Pharmaceuticals. Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID). Retrieved April 29, 2020. Available on the World Wide Web at: https://clinicaltrials.gov/ct2/show/NCT04362137?term=ruxcovid&draw=2&rank=165499 - Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol 2020 Jul;146(1):137-146

How Supplied

Ruxolitinib Oral tablet

Jakafi 5mg Tablet (50881-0005) (Incyte Corporation) null

Ruxolitinib Oral tablet

Jakafi 10mg Tablet (50881-0010) (Incyte Corporation) null

Ruxolitinib Oral tablet

Jakafi 15mg Tablet (50881-0015) (Incyte Corporation) null

Ruxolitinib Oral tablet

Jakafi 20mg Tablet (50881-0020) (Incyte Corporation) null

Ruxolitinib Oral tablet

Jakafi 25mg Tablet (50881-0025) (Incyte Corporation) null

Description/Classification

Description

Ruxolitinib is a kinase inhibitor that inhibits Janus Associated Kinases (JAKs), JAK1 and JAK2. It is indicated for the treatment of adults with intermediate- or high-risk myelofibrosis (e.g., primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis), adults with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea, and patients 12 years and older with steroid-refractory acute graft-versus-host disease. Hematologic toxicity and infection have been reported with ruxolitinib therapy.[46782]

 

Updates for coronavirus disease 2019 (COVID-19):

The use of JAK inhibitors (including ruxolitinib) is being evaluated for the treatment of patients with COVID-19 associated cytokine storm.[65300][65301][65302][65303][65304][65305][65356][65499] An emergency Expanded Access Program has been initiated to allow eligible patients with COVID-19 associated cytokine storm access to ruxolitinib; however, the National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of JAK inhibitors outside of clinical trials because of their broad immunosuppressive effects.[65314]

Classifications

  • Antineoplastic and Immunomodulating Agents
    • Antineoplastics
      • Small Molecule Antineoplastic Janus Associated Kinase (JAKs) Inhibitors
Revision Date: 06/02/2020, 10:39:07 AM

References

46782 - Jakafi (ruxolitinib) tablets package insert. Wilmington, DE: Incyte Corporation; 2020 Jan.65300 - Hochhaus A. Ruxolitinib in COVID-19 Patients With Defined Hyperinflammation (RuxCoFlam). Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04338958?term=Ruxolitinib&cond=COVID&draw=2&rank=365301 - University of Colorado, Denver. Safety and Efficacy of Ruxolitinib for COVID-19. Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04348071?term=Ruxolitinib&cond=COVID&draw=2&rank=165302 - Grupo Cooperativo de Hemopatias Malignas. Treatment of SARS Caused by COVID-19 With Ruxolitinib. Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04334044?term=Ruxolitinib&cond=COVID&draw=2&rank=265303 - University Health Network, Toronto. Study of the Efficacy and Safety of Ruxolitinib to Treat COVID-19 Pneumonia. Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04331665?term=Ruxolitinib&cond=COVID&draw=2&rank=565304 - Fundacion de investigacion HM. Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19. (Ruxo-Sim-20). Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04348695?term=Ruxolitinib&cond=COVID&draw=2&rank=665305 - Novartis Pharmaceuticals. Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness. Retrieved April 20, 2020. Available on the World Wide Web: https://clinicaltrials.gov/ct2/show/NCT04337359?term=Ruxolitinib&cond=COVID&draw=2&rank=465314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed October 9, 2020. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.65356 - Novartis Pharmaceuticals. Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID). Retrieved April 29, 2020. Available on the World Wide Web at: https://clinicaltrials.gov/ct2/show/NCT04362137?term=ruxcovid&draw=2&rank=165499 - Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol 2020 Jul;146(1):137-146

Administration Information

General Administration Information

For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration

  • Administer with or without food.[46782]

Extemporaneous Compounding-Oral

Extemporaneous preparation of oral suspension:

NOTE: Studies have not evaluated the effects of tube feeding on ruxolitinib exposure when administered through a nasogastric tube.

  • Suspend 1 tablet in 40 mL of water by stirring for approximately 10 minutes.
  • Using an appropriate syringe, administer the suspension via a nasogastric tube (size 8 French or larger).
  • The suspension must be administered within 6 hours.
  • Following administration of the suspension, rinse the nasogastric tube with approximately 75 mL of water[46782].

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
    Revision Date: 12/07/2016, 03:47:23 PM

    References

    46782 - Jakafi (ruxolitinib) tablets package insert. Wilmington, DE: Incyte Corporation; 2020 Jan.

    Adverse Reactions

    Mild

    • abdominal pain
    • arthralgia
    • asthenia
    • cough
    • diarrhea
    • dizziness
    • ecchymosis
    • epistaxis
    • fatigue
    • fever
    • flatulence
    • headache
    • infection
    • nausea
    • petechiae
    • pharyngitis
    • pruritus
    • purpura
    • rash
    • vertigo
    • weight gain

    Moderate

    • anemia
    • bleeding
    • constipation
    • cystitis
    • dyspnea
    • edema
    • elevated hepatic enzymes
    • hematoma
    • hypercholesterolemia
    • hypertension
    • hypertriglyceridemia
    • hypotension
    • neutropenia
    • peripheral edema
    • pyuria
    • respiratory depression
    • thrombocytopenia

    Severe

    • abdominal pain
    • anemia
    • diarrhea
    • disseminated intravascular coagulation (DIC)
    • dizziness
    • dyspnea
    • ecchymosis
    • edema
    • elevated hepatic enzymes
    • fatigue
    • headache
    • hematoma
    • hypercholesterolemia
    • hypertension
    • hypertriglyceridemia
    • infection
    • leukoencephalopathy
    • neutropenia
    • new primary malignancy
    • pruritus
    • pyuria
    • thrombocytopenia
    • thrombosis
    • vertigo
    • weight gain

    Hematologic toxicity including anemia (72% to 96%), neutropenia (3% to 58%), and thrombocytopenia (27% to 75%) has been reported in patients who received ruxolitinib in clinical trials. Obtain complete blood counts prior to therapy, every 2 to 4 weeks until the dose is stabilized, and then as clinically indicated. Therapy interruption, a dosage adjustment, and/or blood or platelet transfusions may be necessary in patients who develop severe myelosuppression. Thrombocytopenia (70% vs. 31%), anemia (96% vs. 87%), and neutropenia (19% vs. 4%) occurred in more often in patients with myelofibrosis who received ruxolitinib (n = 155) compared with placebo (n = 151) in a randomized, phase 3 study. Additionally, grade 3 or 4 thrombocytopenia (13%), anemia (45%), and neutropenia (7%) were reported in ruxolitinib-treated patients. Thrombocytopenia (27% grade 3 or 4, less than 6%), anemia (72%; grade 3 or 4, less than 1%), and neutropenia (3%; grade 3 or 4, less than 1%) were reported in patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study. Thrombocytopenia (75% grade 3 or 4, 61%), anemia (75% grade 3 or 4, 45%), and neutropenia (58% grade 3 or 4, 40%) were reported in patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71).[46782]

    Bacterial, mycobacterial, fungal, and viral infections have been reported in patients who received ruxolitinib in clinical trials. Monitor patients for signs and symptoms of infection, especially for tuberculosis and herpes zoster. Initiate treatment (i.e., antibiotic, antifungal, or antiviral medication) promptly in patients who develop an infection. Herpes zoster/post-herpetic neuralgia (2% vs. less than 1%) and urinary tract infection (9% vs. 5%) occurred more often in patients with myelofibrosis who received ruxolitinib (n = 155) compared with placebo (n = 151) in a randomized, phase 3 study. Urinary tract infection included the conditions of cystitis, urosepsis, kidney infection, pyuria, bacteria present in urine, and nitrite present in urine. Herpes zoster infection/post-herpetic neuralgia (6%) and urinary tract infection (less than 6%) were reported in patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study; grade 3 and 4 herpes zoster infection occurred in less than 1% of ruxolitinib-treated patients. Infection (55% grade 3 or 4, 41%) including bacterial infections (32% grade 3 or 4, 28%) and viral infections (31% grade 3 or 4, 14%) were reported in patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71).[46782]

    Bleeding events have been reported in 6% to 49% of patients who received ruxolitinib in clinical trials. In patients with myelofibrosis, hold therapy if bleeding occurs; resume ruxolitinib after the bleeding event has resolved and consider a dose reduction if the underlying cause persists. Bruising/ecchymosis occurred in 23% of patients with myelofibrosis who received ruxolitinib (n = 155) compared with 15% of patients who received placebo (n = 151) in a randomized, phase 3 study. Additionally, grade 3 bruising/ecchymosis was reported in less than 1% of ruxolitinib-treated patients. Bruising included the conditions of contusion, hematoma (injection site hematoma, periorbital hematoma, vessel puncture site hematoma), petechiae, and purpura. Epistaxis was reported in 6% of patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study. Bleeding was reported in 49% of patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71); grade 3 or 4 bleeding occurred in 20% of patients.[46782]

    Dizziness and headache have been reported in patients who received ruxolitinib in clinical trials. Dizziness (18% vs. 7%) and headache (15% vs. 5%) occurred more often in patients with myelofibrosis who received ruxolitinib (n = 155) compared with placebo (n = 151) in a randomized, phase 3 study; additionally, grade 3 dizziness was reported in less than 1% of ruxolitinib-treated patients. Dizziness included the conditions of balance disorder, labyrinthitis, Meniere's Disease, postural dizziness, and vertigo. Dizziness (15%) and headache (16%) were reported in patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study; additionally, grade 3 and 4 headache occurred in less than 1% of ruxolitinib-treated patients. Headache (21%; grade 3 or 4, 4%) and dizziness (16%) were reported in patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71).[46782]

    Weight gain occurred in 7% of patients with myelofibrosis who received ruxolitinib (n = 155) compared with 1% of patients who received placebo (n = 151) in a randomized, phase 3 study. Additionally, grade 3 weight gain was reported in less than 1% of ruxolitinib-treated patients. Weight gain was reported in less than 6% of patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study.[46782]

    Flatulence occurred in 5% of patients with myelofibrosis who received ruxolitinib (n = 155) compared with less than 1% of patients who received placebo (n = 151) in a randomized, phase 3 study. Other gastrointestinal toxicity including abdominal pain (all grade, 15%; grade 3 and 4, less than 1%), constipation (8%), diarrhea (15%), and nausea (6%) was reported in patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study. Diarrhea was reported in 24% of patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71); grade 3 or 4 diarrhea occurred in 7% of patients.[46782]

    Hepatotoxicity has been reported in patients who received ruxolitinib in clinical trials; avoid ruxolitinib in patients with myelofibrosis who have a platelet count of less than 50 X 109 cells/L and hepatic impairment. Patients with GVHD who develop hepatotoxicity may require therapy interruption or a dosage reduction. New or worsening grade 1 elevated hepatic enzymes including increased ALT (25% vs. 7%) and AST (17% vs. 6%) levels occurred more often in patients with myelofibrosis who received ruxolitinib (n = 155) compared with placebo (n = 151) in a randomized, phase 3 study; grade 2 and grade 3 increased ALT levels (1% and 1%) and grade 2 increased AST levels (less tgab1%) were reported in ruxolitinib-treated patients. Additionally, increased ALT levels (all grade, 25%; grade 3, less than 1%) and increased AST levels (23%) were reported in patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study. Increased ALT (48%; grade 3 or 4, 8%) and AST (48%; grade 3 or 4, 6%) levels were reported in patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71).[46782]

    Progressive multifocal leukoencephalopathy (PML) has been reported in patients with myelofibrosis who received ruxolitinib treatment. Consider PML, an opportunistic viral infection of the brain caused by reactivated latent John Cunningham (JC) virus, in the differential diagnosis of patients with new or worsening neurological, cognitive, or behavioral signs or symptoms. Such symptoms include changes in mood, vision, speech, or gait, abnormal thinking, unusual behavior, confusion, memory impairment, and decreased strength on one side of the body. PML is usually diagnosed by brain imaging, cerebrospinal fluid testing for JC viral DNA by polymerase chain reaction, and/or brain biopsy. If PML is suspected, stop treatment with ruxolitinib and evaluate; consider consultation with a neurologist and/or infectious disease specialist. Unfortunately, PML is usually fatal or leads to severe disability, and there are no known effective treatments.[46782]

    There have been reports of patients stopping ruxolitinib during an acute illness after which the patient's clinical course continued to worsen. However, it has not been established whether discontinuation of therapy contributed to the clinical course in these patients. Some patients have experienced fever, respiratory depression, hypotension, disseminated intravascular coagulation (DIC), or multi-organ failure after ruxolitinib discontinuation. Following abrupt discontinuation of ruxolitinib, symptoms of myeloproliferative disease generally return to pretreatment levels in about 1 week. For these reasons, gradual tapering of the dose is recommended with the exception of patients who develop thrombocytopenia or neutropenia. If one or more of these symptoms occur after discontinuation of, or while tapering the dose of ruxolitinib, evaluate for and treat any illness and consider restarting or increasing the dose of ruxolitinib.[46782]

    New primary malignancy has been reported with ruxolitinib therapy, specifically non-melanoma skin cancer such as basal cell, squamous cell, and Merkel cell carcinoma. Periodic skin examinations are recommended; advise patients to report any new or changing lesions.[46782]

    Hypercholesterolemia (e.g., elevated total cholesterol, elevated low-density lipoprotein (LDL) cholesterol) and hypertriglyceridemia have been reported in patients who received ruxolitinib in clinical studies. Obtain a lipid panel and assess triglyceride levels about 8 to 12 weeks after starting ruxolitinib; monitor and treat patients with high cholesterol or triglycerides according to clinical guidelines. New or worsening grade 1 hypercholesterolemia occurred in 17% of patients with myelofibrosis who received ruxolitinib (n = 155) compared with less than 1% of patients who received placebo (n = 151) in a randomized, phase 3 study; grade 2 hypercholesterolemia was reported in less than 1% of ruxolitinib-treated patients. Additionally, hypercholesterolemia (35%) and hypertriglyceridemia (15%) were reported in patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study. Hypertriglyceridemia was reported in 11% of patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71); grade 3 or 4 hypertriglyceridemia occurred in 1% of patients.[46782]

    Asthenia (7%) and fatigue (15%) were reported in patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study. Fatigue was reported in 37% of patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71); grade 3 or 4 fatigue occurred in 14% of patients.[46782]

    Pruritus was reported in 14% of patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study; additionally, grade 3 and 4 pruritus occurred in less than 1% of ruxolitinib-treated patients.[46782]

    Cough (8%), dyspnea/exertional dyspnea (all grade, 13%; grade 3 and 4, 3%) and naso-pharyngitis (9%) were reported in patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study. Dyspnea was reported in 32% of patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71); grade 3 or 4 dyspnea occurred in 7% of patients.[46782]

    Arthralgia (7%) and muscle spasms (12%; grade 3 and 4, less than 1%) were reported in patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study.[46782]

    Edema including peripheral edema was reported in 8% of patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study. Edema was reported in 51% of patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71); grade 3 or 4 edema occurred in 13% of patients.[46782]

    Hypertension was reported in less than 6% of patients with polycythemia vera who received ruxolitinib (n = 110) in a randomized, phase 3 study. Hypertension was reported in 20% of patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71); grade 3 or 4 hypertension occurred in 13% of patients. [46782]

    Rash was reported in 23% of patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71); grade 3 or 4 rash occurred in 3% of patients.[46782]

    Thrombosis was reported in 25% of patients with acute graft-versus-host disease who received ruxolitinib in a single-arm study (n = 71); grade 3 or 4 thrombosis occurred in 11% of patients.[46782]

    Revision Date: 06/18/2019, 03:50:11 PM

    References

    46782 - Jakafi (ruxolitinib) tablets package insert. Wilmington, DE: Incyte Corporation; 2020 Jan.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • abrupt discontinuation
    • anemia
    • bleeding
    • breast-feeding
    • fungal infection
    • hepatic disease
    • hepatitis
    • hypercholesterolemia
    • hypertriglyceridemia
    • infection
    • mycobacterial infection
    • neutropenia
    • new primary malignancy
    • pregnancy
    • progressive multifocal leukoencephalopathy
    • renal disease
    • renal impairment
    • skin cancer
    • thrombocytopenia
    • tuberculosis
    • viral infection

    Hematologic toxicity (e.g., anemia, neutropenia, and thrombocytopenia) has been reported with ruxolitinib therapy. The initial dose is based on platelet count in patients with myelofibrosis. Obtain complete blood counts prior to therapy, every 2 to 4 weeks until the dose is stabilized, and then as clinically indicated. Therapy interruption, a dosage adjustment, and/or blood or platelet transfusions may be necessary in patients who develop severe myelosuppression. In patients with myelofibrosis, hold therapy if bleeding occurs; resume ruxolitinib after the bleeding event has resolved and consider a dose reduction if the underlying cause persists.[46782]

    Serious infections such as tuberculosis (TB), progressive multifocal leukoencephalopathy (PML), bacterial and mycobacterial infection, fungal infection, and viral infection (e.g., herpes zoster) have been reported with ruxolitinib therapy; do not start ruxolitinib in patients with an active infection. Monitor patients for signs and symptoms of infection during therapy and manage promptly. Administer prophylactic antibiotics as appropriate per clinical guidelines. Discontinue treatment if PML is suspected or diagnosed. Increased hepatitis B virus (HBV) viral load with or without elevated transaminase levels has occurred in patients with chronic HBV infection; monitor and treat these patients according to clinical guidelines. Evaluate patients for risk of TB and test patients at higher risk for latent TB; consult with a physician with expertise in treating TB prior to starting ruxolitinib in patients with active or latent TB. Risk factors include history of residence or travel to countries with a high prevalence of TB, close contact with a person with active TB, and a history of active or latent TB where an adequate course of treatment cannot be confirmed.[46782]

    Patients with preexisting hepatic disease may be at increased risk for ruxolitinib-induced adverse events. An initial ruxolitinib dosage reduction may be necessary in patients with baseline hepatic impairment; avoid ruxolitinib in patients with myelofibrosis who have a platelet count of less than 50 X 109 cells/L and hepatic impairment. Monitor complete blood counts more frequently in patients with severe liver graft-versus-host disease (GVHD). Patients with GVHD who develop hepatotoxicity may require therapy interruption or a dosage reduction.[46782]

    Patients with preexisting renal disease may be at increased risk for ruxolitinib-induced adverse events. An initial ruxolitinib dosage reduction may be necessary in patients with baseline renal impairment; avoid ruxolitinib in patients with end-stage renal disease (Creatinine clearance less than 15 mL/min) who do not require dialysis.[46782]

    Avoid abrupt discontinuation of ruxolitinib when stopping the drug for reasons other than thrombocytopenia. Following discontinuation of ruxolitinib, symptoms of myeloproliferative neoplasms generally return to pretreatment levels in about 1 week. There have been reports of patients stopping ruxolitinib during an acute illness after which the patient's clinical course continued to worsen. However, it has not been established whether discontinuation of therapy contributed to the clinical course in these patients. Some patients have experienced fever, respiratory distress, hypotension, DIC, or multi-organ failure after ruxolitinib discontinuation. For these reasons, gradual tapering of the dose is recommended. If one or more of these symptoms occur after discontinuation of, or while tapering the dose of ruxolitinib, evaluate for and treat any illness and consider restarting or increasing the dose of ruxolitinib.[46782]

    New primary malignancy has been reported with ruxolitinib therapy, specifically non-melanoma skin cancer such as basal cell, squamous cell, and Merkel cell carcinoma. Periodic skin examinations are recommended. Advise patients to report any history of skin cancer or if they develop any new or changing lesions during ruxolitinib therapy.[46782]

    Hypercholesterolemia (e.g., elevated total cholesterol, elevated low-density lipoprotein (LDL) cholesterol) and hypertriglyceridemia have been reported with ruxolitinib therapy. The effect of ruxolitinib-induced high cholesterol or high triglycerides on cardiovascular morbidity and mortality is not known. Obtain a lipid panel and assess triglyceride levels about 8 to 12 weeks after starting ruxolitinib; monitor and treat patients with high cholesterol or triglycerides according to clinical guidelines.[46782]

    No well-controlled studies have been conducted evaluating the use of ruxolitinib in pregnant women. Consider the benefits versus the risk of therapy prior to administering ruxolitinib during pregnancy. Animal data involving rats and rabbits administered doses of 15, 30, or 60 mg/kg/day and 10, 30, or 60 mg/kg/day, respectively, during organogenesis, revealed no evidence of teratogenicity. However at doses of 60 mg/kg/day, reductions in fetal weights were observed in both rats and rabbits. Additionally, rabbits experienced an increase in late resorptions when exposed to the 60 mg/kg/day dose.[46782]

    It is not known if ruxolitinib or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because there is a potential for adverse reactions in nursing infants, women should discontinue breast-feeding during ruxolitinib therapy and for at least 2 weeks after the last dose.[46782]

    Revision Date: 06/19/2019, 12:01:17 PM

    References

    46782 - Jakafi (ruxolitinib) tablets package insert. Wilmington, DE: Incyte Corporation; 2020 Jan.

    Mechanism of Action

    Ruxolitinib is a kinase inhibitor that inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2. JAK signaling involves recruitment of signal transducers and activators of transcription to cytokine receptors and activation and subsequent localization of signal transducers and activators of transcription (STAT) to the nucleus, which leads to gene expression modulation. Normally, JAK1 and JAK2 mediate the signaling of several cytokines and growth factors that are important for hematopoiesis and immune function.

    Dysregulated JAK1 and JAK2 signaling has been noted in myelofibrosis and polycythemia vera, which are myeloproliferative neoplasms. In a mouse model of JAK2V617F-positive myeloproliferative neoplasm, oral administration of ruxolitinib prevented splenomegaly, preferentially decreased JAK2V617F mutant cells in the spleen, and decreased circulating inflammatory cytokines such as TNF-alpha and IL-6.

    The JAK-STAT signaling pathway regulates the development, proliferation, and activation of many types of immune cells required for graft-versus-host disease (GVHD) pathogenesis. Decreased expression of inflammatory cytokines in colon homogenates and reduced immune-cell infiltration in the colon were observed in a mouse model of acute GVHD.[46782]

    Revision Date: 06/03/2019, 12:22:09 PM

    References

    46782 - Jakafi (ruxolitinib) tablets package insert. Wilmington, DE: Incyte Corporation; 2020 Jan.

    Pharmacokinetics

    Ruxolitinib is administered orally. The mean steady-state Vd in patients with myelofibrosis and polycythemia vera is 72 L (coefficient of variation (CV), 29%) and 75 L (CV, 23%), respectively. In vitro, it is approximately 97% bound to plasma proteins, mostly to albumin. Ruxolitinib is metabolized primarily by CYP3A4 forming active metabolites (e.g., M18 metabolite). After a single oral radiolabeled dose to healthy adults, elimination was predominately through metabolism with 74% of radioactivity excreted in urine and 22% excreted in feces. Unchanged drug accounted for less than 1% of the excreted total radioactivity. The mean elimination half-life of ruxolitinib is approximately 3 hours, and the mean half-life of ruxolitinib plus metabolites is approximately 5.8 hours. Ruxolitinib clearance was 12.7 L/hour in patients with polycythemia vera (CV, 42%).[46782]

    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C9

    Ruxolitinib is a substrate of the hepatic isoenzymes CYP3A4 (major) and CYP2C9. Inhibitors and inducers of CYP3A4 may alter the pharmacokinetic parameters of ruxolitinib. In vitro, ruxolitinib and its M18 metabolite are not inhibitors of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4. At clinically relevant concentrations, ruxolitinib is not an inducer of CYP1A2, CYP2B6, or CYP3A4, and ruxolitinib and its M18 metabolite are not inhibitors of the P-gp, BCRP, OATP1B1, OATP1B3, OCT1, OCT2, OAT1 or OAT3 transport systems. Ruxolitinib is not a substrate for the P-gp transporter.[46782]

    Route-Specific Pharmacokinetics

    Oral Route

    Ruxolitinib appears to be well absorbed; oral absorption was estimated to be at least 95%. Administration with a high-fat, high-calorie meal does not cause clinically relevant changes in absorption. Maximal ruxolitinib plasma concentrations are achieved within 1 to 2 hours after oral administration. Mean ruxolitinib Cmax and systemic exposure increased proportionally over a single dose range of 5 to 200 mg. Over this ruxolitinib dosage range, the mean Cmax values ranged from 205 to 7,100 nanoMolar (nM) and the AUC values ranged from 862 to 30,700 nM x hour.[46782]

    Special Populations

    Hepatic Impairment

    Following a single oral 25-mg dose, the mean ruxolitinib systemic exposure was increased by 1.9-fold in patients with mild hepatic impairment (Child-Pugh class A), by 1.3-fold in patients with moderate hepatic impairment (Child-Pugh class B), and by 1.7-fold in subjects with severe hepatic impairment (Child-Pugh class C) compared with data from subjects with normal hepatic function. Any degree of hepatic impairment does not clinically impact the pharmacokinetic parameters of ruxolitinib in patients with acute graft-versus-host disease.[46782]

    Renal Impairment

    Following a single oral 25-mg dose, the total systemic exposure of ruxolitinib and its active metabolites was increased by 1.3-fold in subjects with mild renal impairment (CrCl, 60 to 89 mL/min), by 1.5-fold in subjects with moderate renal impairment (CrCl, 30 to 59 mL/min), by 1.9-fold in subjects with severe renal impairment (CrCl, 15 to 29 mL/min), and by 1.6-fold in subjects with end-stage renal disease after dialysis compared with data from subjects with normal renal function (CrCl , 90 mL/min or greater). Ruxolitinib is not removed by dialysis; however, it is not known if some active metabolites are removed by dialysis.[46782]

    Geriatric

    Age does not clinically impact the pharmacokinetic parameters of ruxolitinib.[46782]

    Gender Differences

    Among healthy patients, no significant differences in ruxolitinib pharmacokinetic parameters were observed with regard to gender. In patients with myelofibrosis, clearance was 17.7 L/hr for women and 22.1 L/hr for men; intersubject variability was 39%.[46782]

    Ethnic Differences

    Ethnicity does not clinically impact the pharmacokinetic parameters of ruxolitinib.[46782]

    Obesity

    Weight does not clinically impact the pharmacokinetic parameters of ruxolitinib.[46782]

    Revision Date: 06/03/2019, 12:25:12 PM

    References

    46782 - Jakafi (ruxolitinib) tablets package insert. Wilmington, DE: Incyte Corporation; 2020 Jan.

    Pregnancy/Breast-feeding

    pregnancy

    No well-controlled studies have been conducted evaluating the use of ruxolitinib in pregnant women. Consider the benefits versus the risk of therapy prior to administering ruxolitinib during pregnancy. Animal data involving rats and rabbits administered doses of 15, 30, or 60 mg/kg/day and 10, 30, or 60 mg/kg/day, respectively, during organogenesis, revealed no evidence of teratogenicity. However at doses of 60 mg/kg/day, reductions in fetal weights were observed in both rats and rabbits. Additionally, rabbits experienced an increase in late resorptions when exposed to the 60 mg/kg/day dose.[46782]

    breast-feeding

    It is not known if ruxolitinib or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because there is a potential for adverse reactions in nursing infants, women should discontinue breast-feeding during ruxolitinib therapy and for at least 2 weeks after the last dose.[46782]

    Revision Date: 06/19/2019, 12:01:17 PM

    References

    46782 - Jakafi (ruxolitinib) tablets package insert. Wilmington, DE: Incyte Corporation; 2020 Jan.

    Interactions

    Level 1 (Severe)

    • Upadacitinib

    Level 2 (Major)

    • Amoxicillin; Clarithromycin; Lansoprazole
    • Amoxicillin; Clarithromycin; Omeprazole
    • Atazanavir
    • Atazanavir; Cobicistat
    • Ceritinib
    • Chloramphenicol
    • Clarithromycin
    • Clozapine
    • Cobicistat
    • Conivaptan
    • Darunavir
    • Darunavir; Cobicistat
    • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
    • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
    • Delavirdine
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Fluconazole
    • Fosamprenavir
    • grapefruit juice
    • Idelalisib
    • Indinavir
    • Itraconazole
    • Ketoconazole
    • Lopinavir; Ritonavir
    • Mifepristone
    • Nefazodone
    • Nelfinavir
    • Ombitasvir; Paritaprevir; Ritonavir
    • Posaconazole
    • Ribociclib
    • Ribociclib; Letrozole
    • Ritonavir
    • Saquinavir
    • Telaprevir
    • Telithromycin
    • Tipranavir
    • Tucatinib
    • Voriconazole

    Level 3 (Moderate)

    • Aldesleukin, IL-2
    • Amiodarone
    • Amprenavir
    • Apalutamide
    • Aprepitant, Fosaprepitant
    • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
    • Belladonna Alkaloids; Ergotamine; Phenobarbital
    • Bexarotene
    • Bosentan
    • Carbamazepine
    • Cimetidine
    • Danazol
    • Dexamethasone
    • Diltiazem
    • Dronedarone
    • Drospirenone; Ethinyl Estradiol
    • Drospirenone; Ethinyl Estradiol; Levomefolate
    • Efavirenz
    • Efavirenz; Emtricitabine; Tenofovir
    • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
    • Elbasvir; Grazoprevir
    • Enzalutamide
    • Erythromycin
    • Erythromycin; Sulfisoxazole
    • Ethinyl Estradiol
    • Ethinyl Estradiol; Desogestrel
    • Ethinyl Estradiol; Ethynodiol Diacetate
    • Ethinyl Estradiol; Etonogestrel
    • Ethinyl Estradiol; Levonorgestrel
    • Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate
    • Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
    • Ethinyl Estradiol; Norelgestromin
    • Ethinyl Estradiol; Norethindrone
    • Ethinyl Estradiol; Norethindrone Acetate
    • Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate
    • Ethinyl Estradiol; Norethindrone; Ferrous fumarate
    • Ethinyl Estradiol; Norgestimate
    • Ethinyl Estradiol; Norgestrel
    • Etravirine
    • Fluoxetine
    • Fluoxetine; Olanzapine
    • Flutamide
    • Fluvoxamine
    • Fosphenytoin
    • Imatinib
    • Isavuconazonium
    • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
    • Isoniazid, INH; Rifampin
    • Letermovir
    • Lumacaftor; Ivacaftor
    • Lumacaftor; Ivacaftor
    • Mitotane
    • Modafinil
    • Nafcillin
    • Netupitant, Fosnetupitant; Palonosetron
    • Nevirapine
    • Nicardipine
    • Octreotide
    • Oritavancin
    • Phenobarbital
    • Phenytoin
    • Primidone
    • Ranolazine
    • Rifampin
    • Segesterone Acetate; Ethinyl Estradiol
    • St. John's Wort, Hypericum perforatum
    • Telotristat Ethyl
    • Zafirlukast

    Level 4 (Minor)

    • Trandolapril; Verapamil
    • Verapamil
    Aldesleukin, IL-2: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as aldesleukin, IL-2 a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [2356] [34540] [46782] Amiodarone: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as amiodarone, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] [4950] Amoxicillin; Clarithromycin; Lansoprazole: (Major) Reduce the ruxolitinib dosage during coadministration with clarithromycin in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of clarithromycin or interrupt ruxolitinib treatment during clarithromycin use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. [28238] [46782] Amoxicillin; Clarithromycin; Omeprazole: (Major) Reduce the ruxolitinib dosage during coadministration with clarithromycin in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of clarithromycin or interrupt ruxolitinib treatment during clarithromycin use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. [28238] [46782] Amprenavir: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as amprenavir, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Apalutamide: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with apalutamide; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [46782] [62874] Aprepitant, Fosaprepitant: (Moderate) Use caution if ruxolitinib and aprepitant, fosaprepitant are used concurrently, and monitor for an increase in ruxolitinib-related adverse effects for several days after administration of a multi-day aprepitant regimen. Ruxolitinib is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of ruxolitinib. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Aprepitant is also a CYP2C9 inducer and ruxolitinib is a CYP2C9 substrate. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. [30676] [40027] [46782] Atazanavir: (Major) Reduce the ruxolitinib dosage during coadministration with atazanavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of atazanavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. [28142] [46782] Atazanavir; Cobicistat: (Major) Reduce the ruxolitinib dosage during coadministration with atazanavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of atazanavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. [28142] [46782] (Major) Reduce the ruxolitinib dosage during coadministration with cobicistat in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of cobicistat in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. [46782] [58000] Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with phenobarbital; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [22005] [46782] [55436] [57046] [57048] [57080] Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with phenobarbital; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [22005] [46782] [55436] [57046] [57048] [57080] Bexarotene: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as bexarotene, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [46782] [4791] Bosentan: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as bosentan, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [46782] [5226] Carbamazepine: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with carbamazepine; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [41237] [46782] Ceritinib: (Major) Reduce the ruxolitinib dosage during coadministration with ceritinib in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of ceritinib in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. [46782] [57094] Chloramphenicol: (Major) Reduce the ruxolitinib dosage during coadministration with chloramphenicol in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of chloramphenicol or interrupt ruxolitinib treatment during chloramphenicol use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. [29624] [46782] Cimetidine: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as cimetidine, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [34364] [46782] [57012] Clarithromycin: (Major) Reduce the ruxolitinib dosage during coadministration with clarithromycin in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of clarithromycin or interrupt ruxolitinib treatment during clarithromycin use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. [28238] [46782] Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist. [28262] Cobicistat: (Major) Reduce the ruxolitinib dosage during coadministration with cobicistat in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of cobicistat in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. [46782] [58000] Conivaptan: (Major) Reduce the ruxolitinib dosage during coadministration with conivaptan in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of conivaptan or interrupt ruxolitinib treatment during conivaptan use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; conivaptan is a strong CYP3A4 inhibitor. [31764] [46782] Danazol: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as danazol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [11576] [46782] Darunavir: (Major) Reduce the ruxolitinib dosage during coadministration with darunavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of darunavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. [32432] [46782] Darunavir; Cobicistat: (Major) Reduce the ruxolitinib dosage during coadministration with cobicistat in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of cobicistat in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. [46782] [58000] (Major) Reduce the ruxolitinib dosage during coadministration with darunavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of darunavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. [32432] [46782] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Reduce the ruxolitinib dosage during coadministration with cobicistat in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of cobicistat in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. [46782] [58000] (Major) Reduce the ruxolitinib dosage during coadministration with darunavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of darunavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. [32432] [46782] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Reduce the ruxolitinib dosage during coadministration with ritonavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of ritonavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. [46782] [47165] Delavirdine: (Major) Reduce the ruxolitinib dosage during coadministration with delavirdine in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of delavirdine in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. [28476] [46782] Dexamethasone: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as dexamethasone, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [11334] [46782] [6759] Diltiazem: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as diltiazem, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [11352] [46782] [5004] Dronedarone: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as dronedarone, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [36101] [46782] Drospirenone; Ethinyl Estradiol: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Efavirenz: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as efavirenz, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [46782] [5172] Efavirenz; Emtricitabine; Tenofovir: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as efavirenz, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [46782] [5172] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as efavirenz, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [46782] [5172] Elbasvir; Grazoprevir: (Moderate) Administering ruxolitinib with elbasvir; grazoprevir may result in elevated ruxolitinib plasma concentrations. Ruxolitinib is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events. [46782] [60523] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Reduce the ruxolitinib dosage during coadministration with cobicistat in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of cobicistat in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. [46782] [58000] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Reduce the ruxolitinib dosage during coadministration with cobicistat in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of cobicistat in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. [46782] [58000] Enzalutamide: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with enzalutamide; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [46782] [51727] Erythromycin: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as erythromycin, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Erythromycin; Sulfisoxazole: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as erythromycin, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Desogestrel: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Etonogestrel: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Levonorgestrel: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Norelgestromin: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Norethindrone: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Norgestimate: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Ethinyl Estradiol; Norgestrel: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] Etravirine: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as etravirine, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [33718] [46782] Fluconazole: (Major) Avoid coadministration of ruxolitinib with fluconazole doses greater than 200 mg/day in patients with myelofibrosis (MF) or polycythemia vera (PV). Fluconazole and ruxolitinib may be coadministered at usual doses in patients with acute graft-versus-host disease (GVHD). Taking these drugs together may result in increased ruxolitinib exposure and toxicity. Modify the ruxolitinib as follows in patients with MF or PV who require concomitant use with fluconazole at doses of 200 mg/day or less: In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3; in PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of fluconazole or interrupt ruxolitinib treatment during fluconazole use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; fluconazole is a moderate CYP3A4 inhibitor. [46782] Fluoxetine: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as fluoxetine, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] [5738] [5928] [8873] [8874] Fluoxetine; Olanzapine: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as fluoxetine, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] [5738] [5928] [8873] [8874] Flutamide: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as flutamide, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [34706] [46782] [48644] Fluvoxamine: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as fluvoxamine, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] [8874] Fosamprenavir: (Major) Reduce the ruxolitinib dosage during coadministration with fosamprenavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of fosamprenavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; fosamprenavir is a strong CYP3A4 inhibitor. [29012] [34489] [46782] Fosphenytoin: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with fosphenytoin; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; fosphenytoin is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [22005] [46782] [55436] [56579] [57046] [57048] [57080] [57105] Grapefruit juice: (Major) Avoid the concomitant use of ruxolitinib and grapefruit juice. Increased ruxolitinib exposure is possible if a patient regularly consumes grapefruit/grapefruit juice. [29087] [46782] [58104] Idelalisib: (Major) Reduce the ruxolitinib dosage during coadministration with idelalisib in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of idelalisib in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. [46782] [57675] Imatinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as imatinib, STI-571, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [11372] [46782] [4966] Indinavir: (Major) Reduce the ruxolitinib dosage during coadministration with indinavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of indinavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; indinavir is a strong CYP3A4 inhibitor. [28731] [46782] Isavuconazonium: (Moderate) The plasma concentrations of ruxolitinib may be elevated when administered concurrently with isavuconazonium. Ruxolitinib is a CYP3A4 substrate; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Although a dose adjustment is not necessary when used with drugs that are mild or moderate inhibitors of CYP3A4 such as isavuconazole, monitoring patients for ruxolitinib toxicity may be prudent when these drugs are given concurrently. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days (another moderate CYP3A4 inhibitor). The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] [59042] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with rifampin; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [28840] [29812] [34550] [46782] Isoniazid, INH; Rifampin: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with rifampin; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [28840] [29812] [34550] [46782] Itraconazole: (Major) Reduce the ruxolitinib dosage during coadministration with itraconazole in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur. No initial dose adjustments are necessary for patients with graft-versus-host disease; however, monitor blood counts more frequently for toxicity and adjust the dose of ruxolitinib if necessary. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of itraconazole or interrupt ruxolitinib treatment during itraconazole use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. [46782] Ketoconazole: (Major) Reduce the ruxolitinib dosage during coadministration with ketoconazole as increased ruxolitinib exposure and toxicity may occur. In myelofibrosis (MF) patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In polycythemia vera (PV) patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of ketoconazole or interrupt ruxolitinib treatment during ketoconazole use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. For patients with MF or PV patient stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. In graft-versus-host disease patients, reduce the dose to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. [46782] Letermovir: (Moderate) Plasma concentrations of ruxolitinib could increase when administered concurrently with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. Frequently monitor safety and efficacy of ruxolitinib, and modify dose as needed. Ruxolitinib is a substrate of the enzymes CYP3A4. Letermovir is moderate inhibitor of CYP3A4. When given with cyclosporine, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In a drug interaction study, administration of ruxolitinib with another strong CYP3A4 inhibitor increased ruxolitinib maximum plasma concentration (Cmax) and exposure (AUC) by 33% and 91%, respectively. In addition, ruxolitinib half-life was increased from 3.7 to 6 hours. In another study, administration with a moderate CYP3A4 inhibitor increased ruxolitinib Cmax and AUC by 8% and 27%, respectively. [46782] [62611] Lopinavir; Ritonavir: (Major) Reduce the ruxolitinib dosage during coadministration with ritonavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of ritonavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. [46782] [47165] Lumacaftor; Ivacaftor: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with lumacaftor; ivacaftor; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [46782] [59891] Lumacaftor; Ivacaftor: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with lumacaftor; ivacaftor; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [46782] [59891] Mifepristone: (Major) Reduce the ruxolitinib dosage during coadministration with mifepristone in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of mifepristone or interrupt ruxolitinib treatment during mifepristone use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. [28003] [34716] [46782] [48697] Mitotane: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with mitotane; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; mitotane is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [41934] [46782] Modafinil: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as modafinil, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [46782] Nafcillin: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as nafcillin, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [11312] [11313] [46782] Nefazodone: (Major) Reduce the ruxolitinib dosage during coadministration with nefazodone in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of nefazodone in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. [46782] [48645] [54634] Nelfinavir: (Major) Reduce the ruxolitinib dosage during coadministration with nelfinavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of nelfinavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. [28839] [46782] Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as ruxolitinib. The plasma concentrations of ruxolitinib can increase when co-administered with netupitant; the inhibitory effect on CYP3A4 can last for multiple days. [46782] [58171] Nevirapine: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as nevirapine, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. [46782] [5222] Nicardipine: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as nicardipine, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [11537] [46782] [50341] Octreotide: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as octreotide, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] [5850] Ombitasvir; Paritaprevir; Ritonavir: (Major) Reduce the ruxolitinib dosage during coadministration with ritonavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of ritonavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. [46782] [47165] Oritavancin: (Moderate) Coadministration of oritavancin and ruxolitinib may result in increases or decreases in ruxolitinib exposure and may increase side effects or decrease efficacy of ruxolitinib. Ruxolitinib is primarily metabolized by CYP3A4, but is also metabolized by CYP2C9. Oritavancin weakly induces CYP3A4, while weakly inhibiting CYP2C9. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy. [46782] [57741] Phenobarbital: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with phenobarbital; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [22005] [46782] [55436] [57046] [57048] [57080] Phenytoin: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with phenytoin; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; phenytoin is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [22005] [46782] [55436] [56579] [57046] [57048] [57080] [57105] Posaconazole: (Major) Reduce the ruxolitinib dosage during coadministration with posaconazole in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of posaconazole or interrupt ruxolitinib treatment during posaconazole use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. [32723] [34464] [46782] Primidone: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with primidone; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [22005] [46782] [55436] [56579] [57046] [57048] [57080] Ranolazine: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ranolazine, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [31938] [46782] Ribociclib: (Major) Reduce the ruxolitinib dosage during coadministration with ribociclib in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of ribociclib in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. [46782] [61816] Ribociclib; Letrozole: (Major) Reduce the ruxolitinib dosage during coadministration with ribociclib in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of ribociclib in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. [46782] [61816] Rifampin: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with rifampin; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [28840] [29812] [34550] [46782] Ritonavir: (Major) Reduce the ruxolitinib dosage during coadministration with ritonavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of ritonavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. [46782] [47165] Saquinavir: (Major) Reduce the ruxolitinib dosage during coadministration with saquinavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of saquinavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; saquinavir is a strong CYP3A4 inhibitor. [28995] [39863] [39864] [46782] Segesterone Acetate; Ethinyl Estradiol: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as ethinyl estradiol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] St. John's Wort, Hypericum perforatum: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with St. John's Wort; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; St. John's Wort is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%. [46782] [57202] Telaprevir: (Major) Avoid coadministration of ruxolitinib and telaprevir in patients with platelet counts < 100 x 10^9/L. In patients with platelet counts >= 100 x 10^9/L, ruxolitinib may be administered concurrently with telaprevir if the initial ruxolitinib dose is reduced to 10 mg PO twice daily. Additional dose modification should be made only after close monitoring of ruxolitinib's safety and efficacy. Predictions about the interaction can be made based on the metabolic pathway of ruxolitinib. Ruxolitinib is primarily metabolized by CYP3A4; telaprevir is a potent inhibitor of this isoenzyme. Coadministration may result in a large increase in ruxolitinib serum concentrations, which could cause adverse events such as thrombocytopenia, anemia, neutropenia, or infection. [44393] [46782] Telithromycin: (Major) Reduce the ruxolitinib dosage during coadministration with telithromycin in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of telithromycin or interrupt ruxolitinib treatment during telithromycin use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. [28156] [46782] Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and ruxolitinib is necessary, as the systemic exposure of ruxolitinib may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of ruxolitinib; consider increasing the dose of ruxolitinib if necessary. Ruxolitinib is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate. [46782] [61795] Tipranavir: (Major) Reduce the ruxolitinib dosage during coadministration with tipranavir in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of tipranavir in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; tipranavir is a strong CYP3A4 inhibitor. [31320] [46782] Trandolapril; Verapamil: (Minor) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as verapamil, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] [6446] Tucatinib: (Major) Reduce the ruxolitinib dosage during coadministration with tucatinib in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of tucatinib in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. [46782] [65295] Upadacitinib: (Severe) Concomitant use of ruxolitinib with upadacitinib is not recommended because of the duplication of the mechanism of action (both are Janus kinase inhibitors, also known as JAK inhibitors) and the possibility of increased immunosuppression and increased infection risk. Both drugs are known to cause elevations in hepatic enzymes and gastrointestinal perforation, and a possibility for increased thrombotic risk. [64572] Verapamil: (Minor) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as verapamil, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [46782] [6446] Voriconazole: (Major) Reduce the ruxolitinib dosage during coadministration with voriconazole in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of voriconazole or interrupt ruxolitinib treatment during voriconazole use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; voriconazole is a strong CYP3A4 inhibitor. [28158] [46782] Zafirlukast: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as zafirlukast, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. [2129] [46782] [4948] [7806] [9700]
    Revision Date: 05/02/2020, 02:31:00 AM

    References

    2129 - Katial RK, Stelzle RC, Bonner MW, et al. A drug interaction between zafirlukast and theophylline. Arch Intern Med 1998;158:1713-5.2356 - Piscitelli SC, Vogel S, Figg WD, et al. Alteration in indinavir clearance during interleukin-2 infusions in patients infected with the human immunodeficieny virus. Pharmacotherapy 1998;18:1212-6.4791 - Targretin (bexarotene capsules) package insert. Woodcliff Lake, NJ: Eisai Inc.; 2011 Nov.4948 - Accolate (zafirlukast) package insert. Wilmington, DE: AstraZeneca; 2013 June.4950 - Pacerone (amiodarone) tablets package insert. Maple Grove, MN: Upsher-Smith Laboratories, LLC.; 2018 Nov.4966 - Gleevec (imatinib mesylate) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2014 May.5004 - Cardizem CD (diltiazem) package insert. Bridgewater, NJ: Bausch Health US, LLC.; 2020 Mar.5172 - Sustiva (efavirenz) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 Oct.5222 - Viramune (nevirapine) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2011 Mar.5226 - Tracleer (bosentan) package insert. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2019 May.5738 - Prozac (fluoxetine hydrochloride). Indianapolis, IN: Eli Lilly and Company; 2003 Nov.5850 - Sandostatin (octreotide) package insert. Stein, Switzerland: Novartis Pharma Stein AG Corporation; 2019 April.5928 - DeVane CL, Donovan JL, Liston HL, et al. Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers. J Clin Psychopharmacol. 2004;24:4-10.6446 - Covera-HS (verapamil hydrochloride tablets) package insert. New York, NY: Pfizer Inc.; 2011 Oct.6759 - Dexamethasone tablets USP, Dexamethasone oral solution, and Dexamethasone Intensol (oral solution concentrate) package insert. Eatontown, NJ: West-Ward Pharmaceuticals Corp; 2016 March.7806 - Walsky RL, Gaman EA, Obach RS. Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol 2005;45:68-78.8873 - Brosen K. Some aspects of genetic polymorphism in the biotransformation of antidepressants. Therapie 2004;59:5-12.8874 - Hemeryck A, Belpaire FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. Curr Drug Metab 2002;3:13-37.9700 - Jaakkola T, Backman JT, Neuvonen M, et al. Montelukast and zafirlukast do not affect the pharmacokinetics of the CYP2C8 substrate pioglitazone. Eur J Clin Pharmacol 2006;62:503-9.11312 - Yasuda K, Ranade A, Venkataramanan R, et al. A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos 2008;36:1689-97.11313 - Lang CC, Jamal SK, Mohamed Z, et al. Evidence of an interaction between nifedipine and nafcillin in humans. Br J Clin Pharmacol 2003;55:588-90.11334 - Kovarik JM, Purba HS, Pongowski M, et al. Pharmacokinetics of dexamethasone and valspodar, a P-glycoprotein (mdr1) modulator: implications for coadministration. Pharmacother 1998;18:1230-6.11352 - Cornwell M, Pastan I, Gottesman M. Certain calcium channel blockers bind specifically to multidrug-resistant human KB carcinoma membrane vesicles and inhibit drug binding to P-glycoprotein. J Biol Chem 1987;262:2166-70.11372 - Mahon FX, Belloc F, Lagarde V, et al. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 2003;101:2368-2373.11537 - Katoh M, Nakajima M, Yamazaki H, et al. Inhibitory potencies of 1,4-dihydropyridine calcium antagonists to P-glycoprotein-mediated transport: comparison with the effects of CYP3A4. Pharm Res 2000;17:1189-97.11576 - Konishi H, Takenaka A, Minouchi T, et al. Impairment of CYP3A4 capacity in patients receiving danazol therapy: examination on oxidative cortisol metabolism. Horm Metab Res 2001;33:628-30.22005 - Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol 2006;61(3):246-255.28003 - Mifeprex (mifepristone, RU-486) package insert. New York, NY: Danco Laboratories, LLC; 2019 Apr.28142 - Reyataz (atazanavir) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2020 Sept.28156 - Ketek (telithromycin) package insert. Bridgewater, NJ: Sanofi-Aventis Pharmaceuticals; 2015 Oct.28158 - VFEND (voriconazole) tablets, suspension, and injection package insert. New York, NY: Pfizer Inc; 2020 Sept.28238 - Biaxin (clarithromycin) package insert. North Chicago, IL: AbbVie, Inc.; 2019 Sep.28262 - Clozaril (clozapine) tablets package insert. Rosemont, PA: HLS Therapeutics (USA), Inc. (Clozaril is a registered trademark of Novartis AG); 2017 Feb.28476 - Rescriptor (delavirdine) package insert. Research Triangle Park, NC: ViiV Healthcare; 2012 Aug.28731 - Crixivan (indinavir) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2016 Sept.28839 - Viracept (nelfinavir mesylate) package insert. Research Triangle Park, NC: ViiV Healthcare Company; 2016 Sept.28840 - Niemi M, Backman JT, Fromm MF, et al. Pharmacokinetic interactions with rifampicin [rifampin]. Clin Pharmacokinet 2003;42:819-50.28995 - Invirase (saquinavir) package insert. South San Francisco, CA: Genentech Inc.; 2020 Sept.29012 - Lexiva (fosamprenavir calcium) package insert. Research Triangle Park, NC: ViiV Healthcare; 2019 Mar29087 - Dahan A, Altman H. Food-drug interaction: grapefruit juice augments drug bioavailability-mechanism, extent, and relevance. Eur J Clin Nutr 2004;58:1-9.29624 - Park JY, Kim KA, Kim SL. Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and CYP3A4 in human liver microsomes. Antimicrob Agents Chemother 2003;47:3464-9.29812 - Burman WJ, Gallicano K, Peloquin C. Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibacterials. Clin Pharmacokinet. 2001;40:327-41.30676 - Emend (aprepitant oral products) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2019 Nov.31320 - Aptivus (tipranavir) package insert. Ridgefield, CT: Boehringer Ingelheim; 2020 Jun.31764 - Vaprisol (conivaptan hydrochloride injection) package insert. Deerfield, IL: Baxter Healthcare Corporation; 2016 Oct.31938 - Ranexa (ranolazine extended-release tablets) package insert. Foster City, CA: Gilead Sciences, Inc. 2019 Oct.32432 - Prezista (darunavir) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 May.32723 - Noxafil (posaconazole) package insert. Whitehouse Station, NJ: Merck & Co. Inc.: 2020 Sept.33718 - Intelence (etravirine) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 July.34364 - Humphries TJ, Merritt GJ. Review article: drug interactions with agents used to treat acid-related diseases. Aliment Pharmacol Ther 1999;13:18-26.34464 - Wexler D, Courtney R, Richards W, et al. Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study. Eur J Pharm Sci 2004;21:645-53.34489 - Wire MB, Shelton MJ, Studenberg S. Fosamprenavir clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet 2006;45:137-68.34540 - Sunman JA, Hawke RL, LeCluyse EL, et al. Kupffer cell-mediated IL-2 suppression of CYP3A activity in human hepatocytes. Drug Metab Dispos 2004;32:359-363.34550 - Kuper JI, DAprile M. Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet 2000;39:203-14.34706 - Shet MS, McPhaul M, Fisher CW, et al. Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos 1997;25:1298-303.34716 - Heikinheimo O, Kekkonen R, Lohteenmoki P. The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action. Contraception 2003;68:421-6.36101 - Multaq (dronedarone) package insert. Bridgewater, NJ: Sanofi-aventis; 2014 Mar.39863 - Barry M, Mulcahy F, Merry C, et al. Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection. Clin Pharmacokinet 1999;36:289-304.39864 - Eagling VA, Back DJ, Barry MG. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir, and indinavir. Br J Clin Pharmacol 1997;44:190-194.40027 - Emend (fosaprepitant dimeglumine injection) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2019 Nov.41237 - Tegretol (carbamazepine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2018 Mar.41934 - Lysodren (mitotane) package insert. Princeton, NJ: Bristol-Myers Squibb Oncology; 2017 May.44393 - Incivek (telaprevir) tablet package insert. Cambridge, MA: Vertex Pharmaceuticals, Inc; 2013 Oct.46782 - Jakafi (ruxolitinib) tablets package insert. Wilmington, DE: Incyte Corporation; 2020 Jan.47165 - Norvir (ritonavir tablets, solution, and powder) package insert. North Chicago, IL: AbbVie Inc; 2019 Dec.48644 - Harmsen S, Meijerman I, Beijnen JH, et al. Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009;64:35-43.48645 - Nefazodone tablet package insert. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2015 Sept.48697 - Korlym (mifepristone) tablet package insert. Menlo Park, CA: Corcept Therapeutics Incorporated; 2017 May.50341 - Cardene SR (nicardipine) package insert. Bedminster, NJ: EKR Therapeutics, Inc.; 2016 Aug.51727 - Xtandi (enzalutamide) capsule and tablet package insert. Northbrook, IL:Astellas Pharma US, Inc.; 2020 Aug.54634 - Owen JR, Nemeroff CB. New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone, and mirtazapine. Depress Anxiety 1998;7:24-32.55436 - Patsalos PN, Berry DJ, Bourgeois BF. Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 2008;49:1239-1276.56579 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Updated Mar 10, 2020. Retrieved from the World Wide Web at www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm57012 - Welage LS, Berardi RR. Drug interactions with anti-ulcer agents: considerations in the treatment of acid-peptic disease. J Pharm Pract. 1994;7:177-195.57046 - Perucca E, Hedges A, Makki KA, et al. A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Br J Clin Pharmacol 1984;18:401-10.57048 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Retrieved from the World Wide Web December 27, 2013. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#major57080 - de Leon J, Santoro V, D'Arrigo C, et al. Interactions between antiepileptics and second generation antipsychotics. Expert Opin Drug Metab Toxicol 2012;8:311-34.57094 - Zykadia (ceritinib) package insert. Indianapolis, IN: Novartis; 2019 March.57105 - Schuetz EG, Beck WT, Schuetz JD. Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol 1996;49:311-318.57202 - Zhou S, Chan E, Pan S, et al. Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol 2004;18:262-76.57675 - Zydelig (idelalisib) tablet package insert. Foster City, CA:Gilead Sciences, Inc.; 2018 Oct.57741 - Orbactiv (oritavancin) package insert. Lincolnshire, IL: Melinta Therapeutics, Inc.; 2019 Dec.58000 - Tybost (cobicistat) package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Aug.58104 - Girennavar B, Jayaprakasha GK, and Patil BS. Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. Journal of Food Science. 2007;72(8):C417-C421.58171 - Akynzeo (fosnetupitant; palonosetron) package insert. Lugano, Switzerland: Helsinn Healthcare; 2020 May59042 - Cresemba (isavuconazonium) package insert. Northbrook, IL: Astellas Pharma US, Inc; 2019 Dec.59891 - Orkambi (lumacaftor; ivacaftor) tablet package insert. Boston, MA: Vertex Pharmaceuticals, Inc. 2018 August60523 - Zepatier (elbasvir; grazoprevir) tablet package insert. Whitehouse Station, NJ: Merck, Inc; 2019 Dec.61795 - Xermelo (telotristat ethyl) package insert. The Woodlands, TX: Lexicon Pharmaceuticals, Inc; 2017 Feb.61816 - Kisqali (ribociclib) tablets package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2020 July.62611 - Prevymis (letermovir) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2020 Mar.62874 - Erleada (apalutamide) tablets package insert. Horsham, PA: Janssen Products, LP; 2020 Sept.64572 - Rinvoq (upadacitinib) package insert. North Chicago, IL: Abbvie Inc.; 2020 Jul.65295 - Tukysa (tucatinib) tablets package insert. Bothell, WA: Seattle Genetics, Inc.; 2020 April.

    Monitoring Parameters

    • CBC with differential
    • LFTs
    • platelet count
    • serum creatinine/BUN
    • serum lipid profile
    • serum triglycerides
    • skin cancer screening exam

    US Drug Names

    • Jakafi

    Global Drug names

    Argentina

    • Jakavi - (Novartis)

    Australia

    • Jakavi - (Novartis)

    Austria

    • Jakavi - (Novartis)

    Belgium

    • Jakavi - (Novartis)

    Brazil

    • Jakavi - (Novartis)

    Canada

    • Jakavi - (Novartis)

    Chile

    • Jakavi - (Novartis)

    China

    • Jakavi - (Novartis)

    Czech Republic

    • Jakavi - (Novartis)

    Denmark

    • Jakavi - (Novartis)

    Finland

    • Jakavi - (Novartis)

    France

    • Jakavi - (Novartis)

    Germany

    • Jakavi - (Novartis)

    Greece

    • Jakavi - (Novartis)

    Hong Kong

    • Jakavi - (Novartis)

    Hungary

    • Jakavi - (Novartis)

    Ireland

    • Jakavi - (Novartis)

    Israel

    • Jakavi - (Novartis)

    Japan

    • Jakavi - (Novartis)

    Netherlands

    • Jakavi - (Novartis)

    New Zealand

    • Jakavi - (Novartis)

    Norway

    • Jakavi - (Novartis)

    Poland

    • Jakavi - (Novartis)

    Portugal

    • Jakavi - (Novartis)

    Russian Federation

    • Jakavi - (Novartis)

    Singapore

    • Jakavi - (Novartis)

    Spain

    • Jakavi - (Novartis)

    Sweden

    • Jakavi - (Novartis)

    Switzerland

    • Jakavi - (Novartis)

    Thailand

    • Jakavi - (Novartis)

    Turkey

    • Jakavi - (Novartis)

    Ukraine

    • Jakavi - (Novartis)

    United Kingdom

    • Jakavi - (Novartis)